This work was supported in part by grants from the National Institutes of Health and the Government has certain rights in the invention as a result of this support.
1. Field of the Invention
This invention relates to stimulation of chemotaxis, particularly in relation to prosthetic devices
2. Description of the Prior Art
Replacement of a blood vessel by a prosthetic device is an important and common practice in modern vascular surgery. Although some use is made of veins or arteries taken from other portions of a patient's body, most of such prosthetic devices are prepared from artificial materials that can be prepared in a variety of sizes and stored in a sterile state ready for use.
There are several essential properties of cardiovascular prosthetic materials, among which are the following:
1. Retardation of thrombosis and thromboembolism (antithrombogenic);
2. Minimal harm to blood cells and minimal blood cell adhesion;
3. Long life as prosthetic inserts: and
4. High compliance with the physical and chemical properties of natural blood vessel such as similar elastic modulus and tensile strength.
Another useful property would be a chemotactic response that induced rapid endothelialization and invasion of connective tissue cells for vascular wall reconstruction in a manner such that the prosthesis would be slowly replaced by and/or integrated into newly synthesized internal elastic lamina. None of the materials presently being used can fulfill all of these requirements.
The most commonly used fabric for blood vessel prosthesis is made from Dacron (Trademark, DuPont), a synthetic polyester fiber made from polyethylene terephthalate. Dacron has been used in several weaves and in combination with other materials. An example of a frequently used material is the DeBakey Elastic Dacron fabric manufactured by USCI, a division of C.R. Bard, Inc. (Cat. No. 007830). Other commonly used materials are felted polyurethane and polytetrafluorethylene (Berkowitz et al, Surgery, 72, 221 (1972); Wagner et al, J. Surg. Res., 1, 53 (1956); Goldfarb et al, Trans. Am. Soc. Art. Int. Org., XXIII, 268 (1977)). No chemotactic substance is normally used with these materials.
Another recent development in prosthetic devices is artificial skin of the type disclosed in Yannas and Burke, J. Biomed. Mat. Res., 14, 65-81 (1980). The artificial skin is a collagen/glycosaminoglycan (GAG) composite and had been successfully tested as full-thickness skin wound replacements. Such membranes have effectively protected wounds from infection and fluid loss for long periods of time without rejection and without requiring change or other invasive manipulation. Appropriately designed artificial skin of this type has retarded wound contraction, and the artificial skin has been replaced, at least in part, by newly synthesized connective tissue. Additional disclosure of this artificial skin is found in Yannas et al, ibid, 107-131 (1980), and Dagalakis et al, ibid, 511-528 (1980). No synthetic chemotactic substance is normally used with these materials.
One chemotactic material that might be useful in enhancing invasion of fibroblasts into such prosthetic devices is platelet-derived growth factor (PDGF), a potent fibroblast chemo-attractant. Unfortunately, PDGF cannot be synthesized and must be obtained from platelets, making the utilization of such a material on a wide scale impractical.
Recently, a chemotactic peptide has been identified in tropoelastin and is described in U.S. Pat. No. 4,605,413. This material is a chemotactic peptide having a 6-amino-acid repeating unit of formula APGVGV and its active permutation VGVAPG, in which A represents alanine, P represents proline, G represents glycine, and V represents valine. Although this material readily produces chemotaxis and is a natural component of the human body, therefore making it particularly suitable for use in vivo, room remains for additional improvements in the field of chemotactic stimulation, for example in cell specificity and sensitivity.
Accordingly, there remains a need for an artificial and easily synthesized chemotactic material capable of attracting fibroblasts and endothelial cells into prosthetic devices and thereby enhancing the incorporation of such devices into the regenerating natural tissue.